High Notch1 Expression Correlates with Tumor Stage and Size in Clear Cell Renal Cell Carcinoma

Lee, Jun Nyung; Chun, So Young; Lee, Hyo Jung; Ha, Yun Sok; Kim, Hyun Tae; Yoo, Eun Sang; Kwon, Tae Gyun; Kim, Tae Hwan

Abstract

PURPOSE
Although the influence of Notch signaling on several types of malignancies has been studied, the role of Notch signaling in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we evaluated the levels of Notch1 and Jagged1 and their significance in ccRCC.
MATERIALS AND METHODS
Tumor tissue and matched normal adjacent kidney tissue from 49 ccRCC cases were obtained. The expression of Notch1 and Jagged1 was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. Tissue samples were divided into several groups according to clinicopathological features, and the relative expression of Notch1 and Jagged1 was assessed.
RESULTS
Real-time PCR revealed increased Notch1 expression in tumor tissues compared with that in adjacent normal tissues (p=0.044). Based on the pathological stage, a significant difference in Notch1 expression was observed between tumor and normal kidney tissues in pT2 and pT3 ccRCC (pT2, p=0.041; pT3, p=0.001). Notch1 expression in ccRCC relative to that in normal tissue was higher in later-stage ccRCC and larger ccRCC. Notch1 expression showed significant positive correlation with the maximal diameter of the primary renal tumor (mRNA, p<0.001; protein, p=0.001). High Notch1 expression was associated with recurrence and disease-specific death, although the difference was not significant. Jagged1 level was not significantly correlated with any of the factors examined.
CONCLUSIONS
Notch1 may play a significant role in the tumorigenesis and progression of ccRCC. Notch signaling may be a potential target for chemopreventive or adjuvant therapeutics for ccRCC.